双酚A对成年雄性小鼠的生殖毒性及其作用机制  

Reproductive toxicity of bisphenol A in adult male mice and mechanism

作　　者：郝兴霞[1] 张东泽[1] 于泊洋[2] 张岩[3] 周圆圆[4] 邱雪迎 周好乐[3] 刘陶迪[2] 

机构地区：[1]内蒙古医科大学形态学实验中心,内蒙古呼和浩特010110 [2]内蒙古医科大学心身医学实验室,内蒙古呼和浩特010110 [3]内蒙古医科大学遗传学教研室,内蒙古呼和浩特010110 [4]内蒙古医科大学

出　　处：《吉林大学学报（医学版）》2016年第2期195-199,I0001,共6页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(81260111);内蒙古自治区教育厅高等学校研究项目资助课题(NJZC13439);内蒙古医科大学“英才培育”项目资助课题(2014YCPY002)

摘　　要：目的:探讨双酚A(BPA)对成年小鼠睾丸组织的损伤作用,阐明BPA对动物机体的生殖毒性及其作用机制。方法:8周龄昆明小鼠40只随机分为对照组(玉米油)和低(100 mg·kg^(-1) BPA)、中(200mg·kg^(-1)BPA)、高(400mg·kg^(-1)BPA)剂量BPA组。灌胃染毒4周后,取小鼠睾丸组织,采用流式细胞术检测小鼠睾丸组织中细胞凋亡率;免疫组织化学法检测Fas和FADD蛋白表达情况。结果:与对照组比较,低剂量BPA组小鼠睾丸组织中细胞凋亡率、Fas和FADD阳性细胞表达率无明显变化(P>0.05);中和高剂量BPA组小鼠睾丸组织中细胞凋亡率、Fas和FADD阳性细胞表达率明显升高(P<0.05)。与低剂量BPA组比较,中和高剂量BPA组小鼠睾丸组织中细胞凋亡率、FAS和FADD阳性细胞表达率明显升高(P<0.05);与中剂量BPA组比较,高剂量BPA组小鼠睾丸组织中细胞凋亡率、FAS和FADD阳性细胞表达率明显升高(P<0.05)。中剂量BPA组细胞凋亡率与FAS、FADD阳性细胞表达率呈正相关关系(r=0.430,P<0.05;r=0.238,P<0.01),高剂量组细胞凋亡率与Fas、FADD阳性细胞表达率呈正相关关系(r=0.637,P<0.01;r=0.359,P<0.01)。结论:一定剂量BPA会导致小鼠睾丸组织中细胞凋亡率升高,凋亡调控基因Fas和FADD表达上调;BPA对小鼠睾丸组织有损伤作用,其生殖毒性与激活Fas死亡受体信号通路从而导致细胞过度凋亡有关。Objective.. To investigate the damage effect of bisphenol A （BPA） on the testis tissue of adult mice, and to reveal the reproductive toxicity of BPA in the body of animal and mechanism. Methods： 40 KM mice aged 8 weeks were randomly divided into control group （according to the weight ratio of corn oil gavage）, low dose of BPA group （100 mg- kg-1BPA）, moderate dose of BPA group （200 mg · kg-1BPA）, and high dose of BPA group （400 mg · kg-1BPA）. 4 weeks laster, the testis tissue was taken. The apoptotic rates in the testis tissue were detected by flow cytometry; the distribution and expression of Fas and FADD were measured by immunohistochemistry. Results： Compared with control group, the apoptotie rate, the expression rates of Fas and FADD in testis tissue of the mice in low dose of BAP group had no changes （P〉0.05）, while the apoptotic rates in the testis tissue and the positive expressions rates of Fas and FADD in moderate and high doses of BPA groups were increased （P〈0.05）. Compared with low dose of BPA group, the apoptotic rates and the positive expression rates of FAS and FADD in tests tissue of the mice in moderate and high doses of BPA groups were significantly increased （P〈0.05）. Compared with moderate dose of BPA group, the apoptotic rate and the positive expression rates of FAS and FADD in testis tissue of the mice in high dose of BPA group was significantly increased （P〈0.05）. The overexpression of Fas and FADD was positively correlated to the apoptotic rate in testis tissue in moderate dose of BPA group （r=0. 430, P〈0.05; r=0. 238, P〈0.01） and high dose of BPA group （r=0. 637, P〈0.01; r= 0. 359, P〈0.01）. Conclusion： BPA with content dose can increase the apoptotic rates of cells in testis tissue and the expressions of Fas and FADD. BPA＇ s reproductive toxicity may be closely associated with the activation of Fas signal pathway and resulting in massive apoptosis.

关 键 词：双酚A FAS蛋白 FADD蛋白 细胞凋亡 

分 类 号：R321.1[医药卫生—人体解剖和组织胚胎学]